Iridium-catalyzed allyl-allyl cross-coupling of allylic carbonates with (E)-1,3-diarylpropenes

Article abstract of DOI:10.1039/c5cc04085j

An efficient Ir-catalyzed allyl-allyl cross-coupling reaction of allylic carbonates with (E)-1,3-diarylpropenes was developed to form linear allylated products, 1,5-dienes, regioselectively in excellent yields and with high turnover numbers (up to 2000 S/

Full text of DOI:10.1039/c5cc04085j

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Iridium-Catalyzed Allyl-Allyl Cross-Coupling of
Allylic Carbonates with (E)-1,3-Diarylpropenes
Cite this: DOI: 10.1039/x0xx00000x
Qianjia Yuan,a Kun Yao,b Delong Liub and Wanbin Zhang*a,b
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
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An efficient Ir-catalyzed allyl-allyl cross-coupling reaction of acidity (pKa > 32).9 Generally, the use of weakly acidic compounds
allylic carbonates with ( )-1,3-diarylpropenes was developed (pKa > 25) as pronucleophiles in transition-metal-catalyzed allylic
E
to form linear allylated products, 1,5-dienes, regioselectively substitutions is difficult and it is also hard to control the
in excellent yields and with high turnover numbers (up to regioselectivity of the products.10 To the best of our knowledge the
2000 S/Ir).
use of (E)-1,3-diarylpropenes as pronucleophiles in transition-metal-
catalyzed allylic substitutions or allyl-allyl cross-coupling reactions
has not been reported.
The transition-metal-catalyzed allyl-allyl cross-coupling
reaction is an important method for the preparation of synthetically
useful 1,5-diene products.1-4 Such reactions typically involve the
oxidative addition of allyl esters or allyl halides to a low-valent
metal, followed by transmetalation with allyl nucleophiles and
reductive elimination to give 1,5-diene products. The transmetalation
steps often require the use of toxic allyltin reagents,1 reactive allyl
Grignard reagents,2 allyl boronates3 or allylsilanes.4 These
procedures often generate stoichiometric quantities of hazardous
byproducts that complicate product purification. Therefore, the
development of environmentally benign nucleophiles for the
transmetalation step is highly desired.
Transition-metals such as Ni,3c,5 Cu,2 Pd1a,b; 3a,b,d-f and Au1c have
been used to catalyze allyl-allyl cross-couplings, but the majority of
these procedures provide the desired products with somewhat poor
regioselectivities and/or moderate yields. Iridium catalysts have
shown that they are able to control regioselectivities and
enantioselectivities.6 In 2014, the first example of an Ir-catalyzed
allyl-allyl cross-coupling reaction with allylsilane nucleophiles was
reported by Carreira and co-workers.4b This allyl-allyl cross-
coupling delivered branched products, similar to that of Ir-catalyzed
allylic substitution reactions. In continuation of our efforts to
develop new substrates and nucleophiles for transition-metal-
catalyzed allylic substitution reactions,7 we herein report an efficient
Ir-catalyzed allyl-allyl cross-coupling of allylic carbonates with (E)-
1,3-diarylpropenes for the preparation of linear allylated products,
1,5-dienes. The structure motif of 1,5-diene is found in a variety of
bioactive molecules.8 (E)-1,3-Diarylpropenes have a very weak
Our study began with the following: reaction of tert-butyl
cinnamyl carbonate
1
with 1.5 equivalents of (E)-1,3-
diphenylpropene 2a, in the presence of 1.5 equivalents of DBU, 2.0
mol% of [Ir(cod)Cl]2 and 4.4 mol% of dppf as the catalyst. THF was
used as a solvent and the reaction was performed under a nitrogen
atmosphere at room temperature. However, no product was obtained
even after stirring the reaction mixture overnight (Table 1, entry 1).
Stronger bases were required for the reaction, with NaHMDS
leading to exclusive formation of the linear product 3a (entries 2 and
3). This result contrasts nicely to that of normal Ir-catalyzed allylic
substitutions,6 allyl-allyl cross-couplings4b and allyl-alkene
couplings11 which usually give branched products. Notably, when
KHMDS was used, no product was obtained (entry 4). Several
different ligands were also screened, such as dppe and rac-binap,
and the linear product 3a was obtained in good yields and
regioselectivities (entries 5 and 6). Substrates bearing pivaloyl ester
and methyl carbonate leaving groups gave their corresponding
products in low yields (entries 7 and 8 respectively). THF was found
to be better than other ether-based solvents (entry 3 vs 9-11). The
non-ether solvent toluene gave no product. In the absence of the
iridium catalyst, no product was obtained.
With the optimized reaction conditions in hand (Table 1, entry 3),
electrophile scope was examined (Table 2). Allylic carbonates
bearing electron-withdrawing group F, Cl and Br at the para-
position of the phenyl ring, gave their corresponding products
regioselectively (3b-3d). Substrate bearing F at the para-position of
the phenyl ring gave the product 3b in 97% yield, however,
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Table 1 Optimization of the reaction conditionsa
substrates bearing Cl or Br at the para-position gave only moderate
yields (3c and 3d). Substrates lacking a substituted group or
possessing an electron-donating group at different position of the
phenyl ring, all gave their corresponding products with excellent
yields and regioselectivities (3a and 3e-3h). A Heteroarylallyl
carbonate also reacted smoothly and gave the corresponding product
3i with excellent yield and regioselectivity. Aliphatic allylic
carbonates, possessing conjugated or isolated alkenyl groups, gave
their corresponding products with excellent regioselectivities (3j and
3k). The conjugated alkenyl carbonate gave the product 3j in 94%
yield, while the non-conjugated geranyl carbonate gave the product
3k in a moderate yield.
To further explore the utility of the allyl-allyl cross-coupling, we
studied the scope of the reaction with respect to (E)-1,3-
diarylpropene 2 (Table 3). The catalytic system showed good
compatibility with phenyl groups possessing halogen substituents at
the para-position of the phenyl ring, providing their corresponding
products in 97-99% yields and with 98/2 - >99/1 regioselectivities
(3l-3n). Substrates bearing a methyl or phenyl group at the para-
position of the phenyl ring gave their corresponding products with
high yields and excellent regioselectivities (3o and 3p). Reactions
with (E)-1,3-diphenylpropenes bearing F at the meta- or ortho-
position of the phenyl ring, gave their corresponding products with
excellent yields and regioselectivities (3q and 3r). Substrates
possessing α-naphthyl or β-naphthyl propenes gave their
corresponding products in 94%, 92% yields and with >99/1, 98/2
entry
LG
base
Yield (%)b
3a/4ac
1
2
OBoc
OBoc
DBU
LiHMDS
–
52
–
91/9
3
OBoc
OBoc
OBoc
OBoc
OPiv
NaHMDS
KHMDS
99
–
>99/1
–
4
5d
6e
7
NaHMDS
NaHMDS
NaHMDS
NaHMDS
NaHMDS
NaHMDS
NaHMDS
80
92
trace
50
68
78
95
>99/1
91/9
–
8
9f
10g
11h
OCO2Me
OBoc
OBoc
OBoc
>99/1
95/5
97/3
97/3
a
The reaction was carried out with 1 (0.2 mmol), 2a (0.3 mmol) and base
(0.3 mmol) in THF (2 mL), in the presence of [Ir(cod)Cl]2 (2.0 mol%) and
dppf (4.4 mol%) at room temperature for 3 h under nitrogen unless otherwise
c
noted. b Isolated yields. Determined by 1H NMR analysis. d The ligand was
e
f
dppe (4.4 mol%). The ligand was rac-binap (4.4 mol%). The solvent was
Et2O. g The solvent was 1,4-dioxane. h The solvent was DME.
Table 2 Substrate scope of allylic carbonatesa
Table 3 Substrate scope of (E)-1,3-diarylpropenesa
a
The reaction was carried out with 1 (0.2 mmol), 2a (0.3 mmol) and
aThe reaction was carried out with 1a (0.2 mmol), 2 (0.3 mmol) and
NaHMDS (0.3 mmol) in THF (2 mL), in the presence of [Ir(cod)Cl]2 (2.0
mol%) and dppf (4.4 mol%) at room temperature for 3 h under nitrogen
unless otherwise noted. The yield was for isolated product. The ratio of 3/4
was determined by 1H NMR analysis. bLiHMDS (0.3 mmol) was used instead
of NaHMDS.
NaHMDS (0.3 mmol) in THF (2 mL), in the presence of [Ir(cod)Cl]2 (2.0
mol%) and dppf (4.4 mol%) at room temperature for 3 h under nitrogen
unless otherwise noted. The yield was for isolated product. The ratio of 3/4
1
b
was determined by H NMR analysis. Electrophile 1 (0.3 mmol), 2a (0.2
mmol) and NaHMDS (0.2 mmol) were used, and the yield was based on 2a.
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regioselectivities, respectively (3s and 3t). When allylbenzene was
‡
Electronic Supplementary Information (ESI) available: [details of any
used as the pronucleophile, the desired products were obtained in supplementary information available should be included here]. See DOI:
99% yield and with a ratio of 3:1 linear to branched product.12
To study the efficiency of the catalytic system, the reaction was
carried out with tert-butyl cinnamyl 1a (0.4 mmol), (E)-1,3-
diphenylpropene 2a (0.6 mmol) and NaHMDS (0.6 mmol) in THF
(3 mL), in the presence of 0.05 mol% [Ir(cod)Cl]2 and 0.11 mol%
dppf (S/Ir = 1000; S/Ir = substrate/iridium) at room temperature for
12 h under a nitrogen atmosphere.12 The desired product was
obtained in 90% yield and with >99/1 (linear to branched)
regioselectivity. When the S/Ir ratio was increased to 2000, the
product was obtained in 79% yield after 24 h with no loss of
regioselectivity.
To probe the mechanism of the reaction, we examined whether
the anions generated in the reactions behaved as soft or hard
nucleophiles.13 (E)-1,3-Di(β-naphthyl)propene 2t was reacted with
tert-butyl cis-(5-phenyl-2-cyclohexenyl)carbonate 5, affording only
trans-isomers of 6 with 35% isolated yield (Scheme 1).14 Early
studies examining the stereochemical course of Ir-catalyzed allylic
substitutions showed that the configuration of the products was
predominantly net retention, thus showing an outer sphere
nucleophilic attack with soft nuclophiles.15 Our results suggest that
the reactions involve an inner sphere coordination of the hard 1,3-
diarylallyl nucleophile with the iridium center, followed by reductive
elimination to deliver the desired product, i.e., the reactions proceed
via a cross-coupling pathway rather than an allylic substitution.
10.1039/b000000x/
1
(a) B. M. Trost and E. Keinan, Tetrahedron Lett., 1980, 21,
2595; (b) F. R. van Heerden, J. J. Huyser, D. B. G. Williams and
C. W. Holzapfel, Tetrahedron Lett., 1998, 39, 5281; (c) S.
Porcel, V. López-Carrillo, C. García-Yebra and A. M.
Echavarren, Angew. Chem. Int. Ed., 2008, 47, 1883.
2
3
(a) A. Yanagisawa, N. Nomura and H. Yamamoto, Tetrahedron,
1994, 50, 6017; (b) V. Hornillos, M. Pérez, M. Fañanás-Mastral
and B. L. Feringa, J. Am. Chem. Soc., 2013, 135, 2140.
(a) E. F. Flegeau, U. Schneider and S. Kobayashi, Chem. Eur. J.,
2009, 15, 12247; (b) P. Zhang, L. A. Brozek and J. P. Morken, J.
Am. Chem. Soc., 2010, 132, 10686; (c) A. Jiménez-Aquino, E. F.
Flegeau, U. Schneider and S. Kobayashi, Chem. Commun., 2011,
47, 9456; (d) P. Zhang, H. Le, R. E. Kyne and J. P. Morken, J.
Am. Chem. Soc., 2011, 133, 9716; (e) L. A. Brozek, M. J.
Ardolino and J. P. Morken, J. Am. Chem. Soc., 2011, 133,
16778; (f) M. J. Ardolino and J. P. Morken, J. Am. Chem. Soc.,
2014, 136, 7092.
4
(a) M. Méndez, J. M. Cuerva, E. Gómez-Bengoa, D. J. Cárdenas
and A. M. Echavarren, Chem. Eur. J., 2002, 8, 3620; (b) J. Y.
Hamilton, N. Hauser, D. Sarlah and E. M. Carreira, Angew.
Chem. Int. Ed., 2014, 53, 10759.
5
6
Y. Sumida, S. Hayashi, K. Hirano, H. Yorimitsu and K. Oshima,
Org. Lett., 2008, 10, 1629.
Selected papers of Ir-catalyzed enantioselective allylic
substitutions: (a) J. P. Janssen and G. Helmchen, Tetrahedron
Lett., 1997, 38, 8025; (b) T. Ohmura and J. F. Hartwig, J. Am.
Chem. Soc., 2002, 124, 15164; (c) C. A. Kiener, C. Shu, C.
Incarvito and J. F. Hartwig, J. Am. Chem. Soc., 2003, 125,
14272; (d) O. V. Singh and H. Han, J. Am. Chem. Soc., 2007,
129, 774; (e) S. Spiess, C. Welter, G. Franck, J.-P. Taquet and G.
Helmchen, Angew. Chem., Int. Ed., 2008, 47, 7652; (f) S. T.
Madrahimov, D. Markovic and J. F. Hartwig, J. Am. Chem. Soc.,
2009, 131, 7228; (g) M. Gärtner, S. Mader, K. Seehafer and G.
Helmchen, J. Am. Chem. Soc., 2011, 133, 2072; (h) K.-Y. Ye, H.
He, W.-B. Liu, L.-X. Dai, G. Helmchen and S.-L. You, J. Am.
Chem. Soc., 2011, 133, 19006; (i) W.-B. Liu, C. Zheng, C.-X.
Zhuo, L.-X. Dai and S.-L. You, J. Am. Chem. Soc., 2012, 134,
4812; (j) W.-B. Liu, C. M. Reeves and B. M. Stoltz, J. Am.
Chem. Soc., 2013, 135, 17298; (k) S. Krautwald, M. A.
Schafroth, D. Sarlah and E. M. Carreira, J. Am. Chem. Soc.,
2014, 136, 3020.
For reviews, see: (a) W. Zhang and D. Liu, Chiral Ferrocenes in
Asymmetric Catalysis: Synthesis and Applications; L.-X. Dai and
X.-L. Hou, Eds.; Wiley-VCH: Weinheim, 2010; Chapter 7; (b) N.
A. Butt, D. Liu and Wanbin Zhang, Synlett, 2014, 25, 615;
Selected papers: (c) X. Zhao, D. Liu, H. Guo, Y. Liu and W.
Zhang, J. Am. Chem. Soc., 2011, 133, 19354; (d) M. Quan, N.
Butt, J. Shen, K. Shen, D. Liu and W. Zhang, Org. Biomol.
Chem., 2013, 11, 7412; (e) X. Huo, M. Quan, G. Yang, X. Zhao,
D. Liu, Y. Liu and W. Zhang, Org. Lett., 2014, 16, 1570; (f) X.
Huo, G. Yang, D. Liu, Y. Liu, I. D. Gridnev and W. Zhang,
Angew. Chem., Int. Ed., 2014, 53, 6776.
Scheme 1 Allyl-allyl cross-coupling with inversion of
configuration
In summary, we have developed an efficient Ir-catalyzed allyl-
allyl cross-coupling of allylic carbonates with very weakly acidic
(E)-1,3-diarylpropenes that can be used directly as allyl
pronucleophiles. This transformation proceeded smoothly under
mild conditions to give linear allylated products, 1,5-dienes, with
excellent yields and regioselectivities and with high turnover
numbers (up to 2000 S/Ir).
Notes and references
a
b
School of Chemistry and Chemical Engineering and
School of
Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road,
Shanghai 200240, P. R. China. Fax: 21 5474 3265; Tel: 21 5474 3265; E-
mail: wanbin@sjtu.edu.cn.
7
†
We thank Prof. Tsuneo Imamoto and Dr. Masashi Sugiya of Nippon
Chemical Industrial Co. Ltd for helpful discussions. We also thank one of the
referees for his/her very useful suggestion about the mechanism. This work
was partially supported by the National Natural Science Foundation of China
(No. 21172143, 21232004, 21172145 and 21372152), Program of Shanghai
Subject Chief Scientists (No. 14XD1402300) and Nippon Chemical
Industrial Co. Ltd.
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8
(a) P. J. Belloni, S. Jolidon, M. Klaus and J.-M. Lapierre, New
Gamma Selective Retinoids. WO0183438, 2001; (b) in Terpenes,
Flavors, Fragrances, Pharmaca, Pheromones (Ed.: E.
Breitmaier), Wiley-VCH, Weinheim, 2006.
9
The pKa of (E)-1,3-diarylpropene should be higher than that of
diphenylmethane which is 32.3. See: F. G. Bordwell, W. S.
Matthews and N. R. Vanier, J. Am. Chem. Soc., 1975, 97, 442.
10 (a) B. M. Trost and D. A. Thaisrivongs, J. Am. Chem. Soc.,
2008, 130, 14092; (b) B. M. Trost and D. A. Thaisrivongs, J.
Am. Chem. Soc., 2009, 131. 12056; (c) B. M. Trost, D. A.
Thaisrivongs and J. Hartwig, J. Am. Chem. Soc., 2011, 133,
12439; (d) J. Zhang, C. Stanciu, B. Wang, M. M. Hussain, C.-S.
Da, P. J. Carroll, S. D. Dreher and P. J. Walsh, J. Am. Chem.
Soc., 2011, 133, 20552; (e) S.-C. Sha, J. Zhang, P. J. Carroll and
P. J. Walsh, J. Am. Chem. Soc., 2013, 135, 17602.
11 J. Y. Hamilton, D. Sarlah and E. M. Carreira, J. Am. Chem. Soc.,
2014, 136, 3006.
12 Please see the supporting information.
13 The mechanism of allylic substitution, for Pd see: (a) B. M.
Trost and M. L. Crawley, Chem. Rev. 2003, 103, 2921; For Ir
see: (b) S. T. Madrahimov and J. F. Hartwig, J. Am. Chem. Soc.
2012, 134, 8136.
14 Soft nucleophiles result in net retention via double inversion
whereas hard nucleophiles react by single inversion. Examples
see Ref. 10.
15 (a) R. Takeuchi and M. Kashio, Angew. Chem. Int. Ed. Engl.,
1997, 36, 263; (b) B. Bartels, C. García-Yebra, F. Rominger and
G. Helmchen, Eur. J. Inorg. Chem., 2002, 2002, 2569.
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